SUBJECTS Curtius reactions

Very few imidazo[4,5-b] pyrazines have been reported in the literature1-3 and no good general method has been available for preparing compounds in this most interesting heterocyclic class. We have found that the Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide (Scheme I) proceeds with intramolecular cyclization to provide, in good yield, a wide variety of the subject compounds. We will report here only the 6-substituted 5-chloro-l, 3-dihydro-2tf-... 

Reaction procedures affect the products when malonic acid half-esters (75) with an acidic hydrogen at the a-position are subjected to the modified Curtius reaction. - The usual one-pot procedure, in which alcohols are present from the beginning, affords esters (76), whereas the two-in-one procedure, in which... 

COMPOUNDS SUBJECTED TO THE CURTIUS REACTION Auphatic Acid Demvatives... 

COMPOUNDS SUBJECT TO THE CURTIUS REACTION-Coniinued Aliphatic Acid Debivatites—Cmtinued... 

The fundamental subject of this section is the transformation of A -pyrazolines into cyclopropanes (Buchner-Curtius and Kishner cyclopropane syntheses). The cyclopropane is often accompanied by alkenes (67HC(22)l). When applied to A -pyrazolines the reaction occurs via the A isomers (Scheme 37). 

An extensive review of the chemistry of aliphatic and aromatic azides is given by Boyer and Canter [167] and Gray [168]. Organic azides are subject to various reactions such as the Bergmann degradation and the synthesis of peptides, the well known Curtius rearrangement, the Darapsky synthesis of a-aminoacids [169], for synthesis of triazoles [170], tetrazoles ( Schmidt reaction ) [169] and [171] etc. These reactions lie beyond the scope of the present book. 

An alternate route to substituted tetrahydrobenzazepines (Scheme 33) commenced with the Michael addition of the ester 351 to acrylonitrile in the presence of Triton B, and the intermediate cyanoester was converted to 352 by reduction of the ester function with lithium borohydride and O-benzylation (168). Base-induced hydrolysis of the nitrile group of 352 delivered the corresponding acid, which was transformed to 353 via a Curtius rearrangement. Subjection of 353 to a modified two-step Tschemiac-Einhom reaction involving AMiydroxymethyla-tion and subsequent acid-catalyzed cyclization gave 354. 

The reaction sequence of Figure 11.40 shows how a carboxylic acid (which can be prepared by saponification of the methyl ester that is accessible according to Figure 9.6) can be subjected to a Curtius degradation in a one-pot reaction. This one-pot procedure is convenient because there is no need to isolate the potentially explosive acyl... 

N-oxide 220, which with acetic anhydride afforded the acetate 22L Treatment of 221 first with KaCOs/MeOH and then with SOCI2 led to the formation of chloride 222. Reaction of 222 with A -cyanomethylpyrrolidine gave the quaternary salt 223, which was, without isolation, converted into aldehyde 224 by treating first with f-BuOK and then with oxalic acid. Oxidation of 224 with pertrifiuoroacetic acid and then further oxidation of the N-oxide product with KMn04 gave the carboxylic acid 225. This compound was subjected to the Yamada modification of the Curtius rearrangement, then hydrolysis, to provide the amine 226. Treatment of 226 with... 

They commenced their efforts by subjecting the cyclohexanone 84 to a Fischer indoUzation to furnish indolenine 85. A Curtius rearrangement and a hydrolysis protocol then converted the carboxylic acid to amine 86, which undergoes cyclization during the course of the reaction to render tetracychc pyrroloindole 82. 

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